The brain usefully organizes sensory information by building internal representations of the external world. These internal sensory maps are read by higher neural centers that can trigger learned and innate behaviors, emotions, thoughts and memories. For nearly all animals the most important information in the outside world comes not from sights or sounds but smells - volatile chemical odorants that inform animals about the proximity of food, the availability of appropriate mates or the lurking danger of a nearby predator. The overarching goal of this grant is to identify general principles about how the brain usefully organizes sensory information by specifically exploring the neural wiring that underlies olfaction. Odors are detected within the nose by olfactory sensory neurons, whose axons project to structures in the olfactory bulb called glomeruli. Each glomerulus is a discrete information channel that is innervated by the dendrites of projections neurons whose axons terminate in the higher brain. As olfactory information passes from the sensory epithelia in the nose, through the olfactory bulb, and into the cortex, it is formatted and transformed to enable appropriate behavioral responses. But despite the fact that olfaction is the sensory modality that enables most animals to interact with their environment, we know little about how the olfactory system usefully organizes information within the cortex, in part because to date it has been technically difficult to trace axonal projections from identified glomeruli in the bulb to their targets in the brain. Here we propose to deploy a new method we have developed that enables high-precision targeted labeling of single glomeruli and their associated neurons. We will use this approach to reveal how information about odorants in the environment is transformed as it passes from the olfactory bulb to the cortex (Aim I). We will then use a combination of behavioral analysis, functional imaging, genetics and optogenetics to ask whether the olfactory circuits that are dedicated to driving innate behaviors (such as attraction or avoidance) are segregated from those involved in sensing general odors (Aim II). Taken together this work will reveal the core organizational logic of the olfactory system, suggesting models for how the brain discriminates odors and generates odor-driven learned and innate behaviors. These experiments will also identify neural substrates upon which experience, expectation and emotion - as well as disease - can act to alter perception. PUBLIC HEALTH RELEVANCE: Here we propose to deploy a novel neural circuit tracing technique we have developed to reveal how the brain meaningfully organizes sensory information from the outside world to facilitate innate and learned behaviors. We will describe how neural information is formatted and transformed as it flows from the nose, through multiple processing stages, and into the higher brain where behaviors are generated. These experiments will lead to insights into how the architecture of neural circuits influences brain function, thereby improving our understanding of neural physiology and offering a window into how pathological damage might alter information processing and behavior.